EMD 53998 acts as Ca2+-sensitizer and phosphodiesterase III-inhibitor in human myocardium

The effect of EMD 53998 (EMD) (0.1–100 μmol/l), chemically a racemic thiadiazinone derivative, suggested to be a potent Ca2+-sensitizer, was studied in human failing and nonfailing left ventricular myocardium. For comparison, the effects of the pyridazinone derivative pimobendan (0,1–300 μmol/l), isoprenaline (Iso) (0.001–3 μmol/l) as well as CaCl2 (1.8–1.5 mmol/l Ca2+) were investigated. The positive inotropic response were examined in electrically driven (1 Hz, 37°C) human left ventricular papillary muscle strips from terminally failing hearts (NYHA IV, n=24) and nonfailing donor hearts (NF, n=9). The effect of EMD on the Ca2+-sensitivity of skinned fiber preparations from the very same human failing hearts were studied as well.